This invention relates to intraluminal vascular grafts, commonly referred to as stents, and more particularly concerns a method for delivery of radioactive stents.
After a vessel has undergone treatment by percutaneous transluminal coronary angioplasty (PTCA), restenosis or narrowing of the vessel may occur. Two known contributors to restenosis are intimal hyperplasia, the formation of neointimal cells within the vessel, and vessel remodeling. Expandable stents are implanted within vessels in an effort to maintain vessel patency by preventing collapse and/or by impeding restenosis. Implantation of a stent is typically accomplished by mounting the stent on the inflatable portion of a balloon catheter, maneuvering the catheter through the vasculature so as to position the expandable stent at the desired location within a body lumen, and immediately inflating the balloon to expand the stent so as to engage the lumen wall. The stent returns to a predetermined shape in an expanded configuration allowing the balloon to be deflated and the catheter to be removed to complete the implantation procedure. However, restenosis after stent implantation may also occur.
Previously devised approaches to inhibit restenosis include intravascular radiation therapy also known as vascular brachytherapy. One such approach utilizes an expandable stent coated or imprinted with a radioactive isotope. The radioactive stent may be implanted in the same manner as a non-radioactive stent. Upon the immediate expansion of the radioactive stent to engage the vessel wall, the treated tissue receives a radiation dose for a time period defined by the radiation source chosen and its associated half-life. The delivered radiation dose results in localized cell kill at the treated site, thus inhibiting restenosis.
The radiation source may be either a gamma-emitting or a beta-emitting radioisotope. Radiation from a beta-emitting radioisotope diminishes rapidly with distance from the source thus delivering minimal energy at more than two millimeters. A beta-emitting radioisotope presents several advantages over a gamma-emitting radioisotope particularly in areas of safety of catheter laboratory personnel and ease of storage. On the other hand, a gamma-emitting radioisotope offers more penetration and can improve dose homogeneity.
Another approach to inhibit restenosis involves the exposure of the vasculature to an initial dose rate of high energy radiation followed by a second dose rate of lower energy radiation. Stents are imprinted with multiple radioisotopes in order to achieve the desired dosimetry. Multiple isotope radioactive stents are implanted in the vasculature in the same manner as single isotope radioactive stents and non-radioactive stents. This method includes positioning the stent in the target area and immediately deploying the stent to engage the vessel walls.
However, both single and multiple isotope radioactive stents have been associated with a xe2x80x9ccandy wrapper effectxe2x80x9d caused by the inhibition of cell growth in the middle of the stent and neointimal cell proliferation at the distal and proximal ends of the stent. This xe2x80x9ccandy wrapper effectxe2x80x9d may be caused by the delivery of a higher delivered dose in the middle of the stent resulting in cell kill in the middle region and delivery of a lower radiation dose at the ends of the stent which may inhibit, but to a lesser extent, neointimal cell formation.
Another approach for inhibiting restenosis involves delivering radiation using percutaneous intravascular catheters. A radiation source wire is inserted into a catheter lumen and the radiation source wire is advanced to the target region where the lesion is irradiated. After radiation therapy, the radiation source wire is withdrawn from the catheter. One of the problems associated with this method is ensuring the delivery of a circumferentially uniform dose to the target area. Since the radiation source wire is inserted through the catheter lumen, curvature in the catheter lumen or eccentricity at the target site can affect the uniformity of the dose delivered to the target area.
The above approaches for delivery of radiation potentially exhibit non-uniformity in the radiation dose delivered to the target area. Generally, a non-uniform radiation dose is characterized by uneven radiation doses delivered to the target area. An uneven radiation dose is typically further characterized by relatively high radiation doses also known as xe2x80x9chot spotsxe2x80x9d and relatively low radiation doses also known as xe2x80x9ccold spotsxe2x80x9d being delivered within the target area.
A radioactive stent is typically constructed as a metal alloy mesh. The radioactive stent may be imprinted with a given radioisotope by bombardment of the stent with radioactive ions. Thus, the radioisotope is imprinted into the stent metal alloy. Once the stent is expanded, the mesh structure of the stent creates void areas adjacent to the metal alloy such that only approximately twenty percent of the vessel wall tissue in the target area is in contact with the metal alloy. Since radiation is attenuated with distance, tissue regions closer to the metal alloy receive a much higher dose of radiation than the tissue regions that are in the adjacent void areas. Thus, the tissue may receive a non-uniform pattern of radiation based upon the location of the expanded metal alloy mesh. The variation of absorbed radiation dose of the targeted tissue may contribute to the unfavorable vascular/cellular responses sometimes seen with radioactive stents.
Accordingly, a new method for uniform dose radioactive stent delivery is required.
The present invention provides a method for delivering multiple radioisotopes to a target area of a vessel and allowing the radioisotopes to dwell in the target area for a period of time to deliver a predetermined and uniform dose of radiation.